Research Topics
Genomes and Genes
| KEITH T BURRIDGESummaryAffiliation: University of North Carolina Country: USA Publications
Research Grants
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Detail Information
Publications
The tension mounts: Stress fibers as force-generating mechanotransducersKeith Burridge
Department of Cell Biology and Physiology, 2 Lineberger Comprehensive Cancer Center, and 3 McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599
J Cell Biol 200:9-19. 2013..Although SFs are superficially similar in organization to the sarcomeres of striated muscle, there are intriguing differences in their organization and behavior, indicating that much still needs to be learned about these structures...
Regulation of cell adhesion by protein-tyrosine phosphatases. I. Cell-matrix adhesionKeith Burridge
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 281:15593-6. 2006..In addition, high levels of protein tyrosine phosphorylation generally promote disassembly or turnover of adhesions. In this brief review, we will discuss the role of protein-tyrosine phosphatases in cell-matrix adhesions...- Rho and Rac take center stageKeith Burridge
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
Cell 116:167-79. 2004..Additionally, we will discuss how there is signaling crosstalk between family members and how various bacterial pathogens have developed strategies to manipulate Rho protein activity so as to enhance their own survival... - RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migrationJaap D van Buul
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
J Cell Biol 178:1279-93. 2007..Together, these results identify a new signaling pathway involving RhoG and its exchange factor SGEF downstream from ICAM1 that is critical for leukocyte TEM... - Cadherin engagement inhibits RhoA via p190RhoGAPNicole K Noren
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill 27599, USA
J Biol Chem 278:13615-8. 2003..The inhibition of RhoA activity by cadherins was antagonized by expression of a dominant negative p190RhoGAP. Taken together, these data demonstrate that p190RhoGAP activity is critical for RhoA inactivation by cadherins... - XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoCWilliam T Arthur
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 277:42964-72. 2002..In conclusion, here we describe a Rho family GEF that can discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving insight to the divergent functions of these three proteins... - Rnd proteins function as RhoA antagonists by activating p190 RhoGAPKrister Wennerberg
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Curr Biol 13:1106-15. 2003..However, effector molecules of Rnd proteins with such properties have not been identified... - A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectinAdi D Dubash
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill NC 27599, USA
J Cell Sci 120:3989-98. 2007..These data establish a previously uncharacterized role for the exchange factors Lsc/p115 RhoGEF and LARG in linking fibronectin signals to downstream RhoA activation... - IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entryKris A DeMali
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 281:39534-41. 2006..The combination of these two effects, namely weakened adhesion and increased contractility, account for the loss of actin stress fibers and cell rounding observed in cells exposed to IpaA... - Endogenous RhoG is rapidly activated after epidermal growth factor stimulation through multiple guanine-nucleotide exchange factorsThomas Samson
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA
Mol Biol Cell 21:1629-42. 2010..Finally, we present results that show that RhoG has functions in EGF-stimulated cell migration and in regulating EGF receptor internalization... - Analysis of activated GAPs and GEFs in cell lysatesRafael Garcia-Mata
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
Methods Enzymol 406:425-37. 2006..This assay can be used to identify GEFs, GAPs, and effectors involved in specific cellular pathways to determine their GTPase specificity and to monitor the temporal activation of GEFs and GAPs in response to upstream signals... - VEGF-induced Rac1 activation in endothelial cells is regulated by the guanine nucleotide exchange factor Vav2Tiana A Garrett
Department of Cell and Developmental Biology, University of North Carolina Chapel Hill, Lineberger Comprehensive Cancer Center, Campus Box 7295, Chapel Hill, NC 27599, USA
Exp Cell Res 313:3285-97. 2007..Finally, we show that depressing Vav2 expression by siRNA impairs VEGF-induced endothelial cell migration. Taken together, our results provide evidence that Vav2 acts downstream of VEGF to activate Rac1... - Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of RhoMartin P Playford
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Exp Cell Res 314:3187-97. 2008..Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho... - SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosisShawn M Ellerbroek
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Mol Biol Cell 15:3309-19. 2004..Together, this work establishes SGEF as a RhoG exchange factor and provides evidence that both SGEF and RhoG regulate membrane dynamics in promotion of macropinocytosis... - Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edemaGiorgio Zanotti
Division of Cardiothoracic Surgery, Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7065, USA
Am J Physiol Lung Cell Mol Physiol 297:L52-63. 2009..This may be due to a novel mechanism: regulation of endothelial cell cytoskeleton affecting microvascular endothelial cell permeability... - Regulation of cell adhesion by protein-tyrosine phosphatases: II. Cell-cell adhesionJennifer L Sallee
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA
J Biol Chem 281:16189-92. 2006..This review will discuss the role of protein-tyrosine phosphatases in cell-cell interactions, with an emphasis on cadherin-mediated adhesions... - ICAM-1-mediated, Src- and Pyk2-dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migrationMichael J Allingham
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
J Immunol 179:4053-64. 2007..7 +/- 7.1% and 38.8 +/- 6.5% reduction, respectively). Our results demonstrate that engagement of ICAM-1 by leukocytes results in tyrosine phosphorylation of VE-cadherin, which is required for efficient neutrophil TEM... - RhoG signals in parallel with Rac1 and Cdc42Krister Wennerberg
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:47810-7. 2002..Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors... - The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activityRafael Garcia-Mata
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, 12 026 Lineberger, CB 7295, Chapel Hill, NC 27599, USA
Mol Cell Biol 27:8683-97. 2007..Together, our results suggest that the interaction between Net1 and Dlg1 may contribute to the mechanism of Net1-mediated transformation... - Density-enhanced phosphatase 1 regulates phosphorylation of tight junction proteins and enhances barrier function of epithelial cellsJennifer L Sallee
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 284:14997-5006. 2009..These data suggest that DEP-1 can modify the phosphorylation state of tight junction proteins and play a role in regulating permeability... - Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motifAmir Aghajanian
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America
PLoS ONE 4:e8045. 2009..We hypothesized that this redox-based mechanism occurs in cells and affects cytoskeletal dynamics, and in this report we conclude this is indeed a novel mechanism of regulating the GTPase RhoA... - The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen speciesElizabeth Monaghan-Benson
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 284:25602-11. 2009..Collectively, these data suggest that VEGF leads to a Rac-mediated generation of ROS, which, in turn, elevates the tyrosine phosphorylation of VE-cadherin and beta-catenin, ultimately regulating adherens junction integrity... 
Analysis of low molecular weight GTPase activity in endothelial cell culturesErika S Wittchen
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Methods Enzymol 443:285-98. 2008..In this chapter, we describe the techniques for in vitro assessment of GTPase activity in endothelial cells grown in monolayer culture as a model system for studying their role during angiogenesis...- Def-6, a guanine nucleotide exchange factor for Rac1, interacts with the skeletal muscle integrin chain alpha7A and influences myoblast differentiationThomas Samson
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 282:15730-42. 2007..Thus, our data suggest a role for Def-6 in the fine regulation of Rac1 during myogenesis with the integrin alpha7A chain guiding this regulation in a spatio-temporal manner... - Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1Lynda J Peterson
Department of Ophthalmology, 6135 Neuroscience Research Building, University of North Carolina, 103 Mason Farm Road, CB 7041, 6135 NSRB, Chapel Hill, NC 27599 7041, USA
Exp Eye Res 84:737-44. 2007..We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD... - Serine phosphorylation negatively regulates RhoA in vivoShawn M Ellerbroek
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:19023-31. 2003.... - Coupling membrane protrusion and cell adhesionKris A DeMali
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA
J Cell Sci 116:2389-97. 2003..However, there are also physical links between the cellular machineries that mediate cell adhesion and membrane protrusion, such as vinculin... - RhoA is required for cortical retraction and rigidity during mitotic cell roundingAmy Shaub Maddox
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
J Cell Biol 160:255-65. 2003..Cumulatively, these results suggest that the mitotic increase in RhoA activity leads to rearrangements of the cortical actin cytoskeleton that promote cortical rigidity, resulting in mitotic cell rounding... - Integrin signaling to the actin cytoskeletonKris A DeMali
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
Curr Opin Cell Biol 15:572-82. 2003..Integrins promote actin assembly via the recruitment of molecules that directly activate the actin polymerization machinery or physically link it to sites of cell adhesion... - Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesionKris A DeMali
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
J Cell Biol 159:881-91. 2002..The recruitment of the Arp2/3 complex to vinculin may be one mechanism through which actin polymerization and membrane protrusion are coupled to integrin-mediated adhesion... - Simultaneous stretching and contraction of stress fibers in vivoLynda J Peterson
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Mol Biol Cell 15:3497-508. 2004..In the periphery, the banding patterns for both proteins were shorter, whereas in central regions, where stretching occurred, the bands were wider... - Trading spaces: Rap, Rac, and Rho as architects of transendothelial migrationErika S Wittchen
Department of Cell and Developmental Biology, Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7090, USA
Curr Opin Hematol 12:14-21. 2005..This review focuses on recent developments in understanding regulation of leukocyte transendothelial migration by small GTPase signaling... - Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier functionErika S Wittchen
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 280:11675-82. 2005..Furthermore, these results suggest that Rap1 may be a novel therapeutic target for clinical conditions in which an inappropriate inflammatory response leads to disease... - Regulation of Rho family GTPases by cell-cell and cell-matrix adhesionWilliam T Arthur
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
Biol Res 35:239-46. 2002.... - PTP-PEST controls motility through regulation of Rac1Sarita K Sastry
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
J Cell Sci 115:4305-16. 2002..Our data suggest a model in which PTP-PEST is activated by integrins and localized to regions where it can control motile events at the leading edge through inhibition of the small GTPase Rac1... - Catching a GEF by its tailRafael Garcia-Mata
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 12 026 Lineberger, CB 7295, Chapel Hill, NC 27599, USA
Trends Cell Biol 17:36-43. 2007..Here, we summarize recent data that highlight the importance of these interactions in Rho-GEF regulation... - RhoA and ROCK promote migration by limiting membrane protrusionsRebecca A Worthylake
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center and Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:13578-84. 2003..Together, our results show that RhoA/ROCK signaling promotes migration by restricting integrin activity and membrane protrusions to the leading edge... - In vitro modeling of nonhypoxic cold ischemia-reperfusion simulating lung transplantationMonica Casiraghi
Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
J Thorac Cardiovasc Surg 138:760-7. 2009..We developed an in vitro model of nonhypoxic ischemia-reperfusion injury to simulate these events... - Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1Etienne Boulter
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Nat Cell Biol 12:477-83. 2010.... - Chapter 1. Focal adhesions: new angles on an old structureAdi D Dubash
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, CB 7295, University of North Carolina, Chapel Hill, NC 27599, USA
Int Rev Cell Mol Biol 277:1-65. 2009..Throughout this chapter, we have highlighted areas of focal adhesion biology where major questions still remain to be answered...
Research Grants
- STRUCTURE AND FUNCTION OF FOCAL ADHESIONSKeith Burridge; Fiscal Year: 1993..These studies should provide an understanding of the structural organization of FAs, the regulation of their assembly and disassembly, and their role in signalling from the ECM...
- STRUCTURE/FUNCTION OF FOCAL ADHESIONSKeith Burridge; Fiscal Year: 2000..The effect of vinculin on PIP2 hydrolysis will be studied. We will determine which domain of vinculin restores anchorage-dependent growth when transfected into cells with reduced vinculin expression. ..
- Structure and Function of Fiscal AdhesionsKeith Burridge; Fiscal Year: 2004....
- Cell Adhesion and the Regulation of Rho GTPasesKeith Burridge; Fiscal Year: 2007..Proteins with PDZ domains are typically enriched in cell-cell junctions. We will determine whether the binding of GEFs to PDZ domains serves to recruit them to cell junctions and whether this interaction regulates their activity. ..
- Adhesion and Migration in InflammationKeith Burridge; Fiscal Year: 2007..abstract_text> ..
- ACTIN-MEMBRANE INTERACTIONKeith Burridge; Fiscal Year: 1992..New components identified by these antibodies will be purified and characterized...
- Cell Adhesion and the Regulation of Rho GTPasesKeith Burridge; Fiscal Year: 2010..We will determine whether the binding of GEFs to PDZ domains serves to recruit them to cell junctions and whether this interaction regulates their activity. ..